Considerable data have documented the key role of the kidney in pathophysiology of hypertension and the likelihood that alterations in adrenergic response occurs in experimental and clinical hypertension. We propose to test the hypothesis that changes in renal adrenergic receptors and/or signal transduction by adrenergic receptors contribute to the pathogenesis of hypertension. A variety of new approaches will be used to examine: 1) properties and distribution of renal alpha- adrenergic receptor subtypes. 2) signal transduction of renal alpha1- adrenergic receptors, with the focus on generation of arachidonic acid products in parallel with phosphoinositide hydrolysis; 3) adrenergic receptor and G protein MRNA levels to be assessed by Northern blotting and resolution hybridization assay. We will utilize these methodologies to assess changes in adrenergic receptors and signal transduction in 3 rat models of hypertension: SHR, DOCA-saline, and salt-sensitive Dahl hypertension. These models should provide the opportunity to assess both genetic and acquired forms of hypertension. The proposed studies should provide new insights regarding renal adrenergic receptors and the possible mechanisms regulating these receptors in normal and hypertensive animals.
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